Franco Renato, Zappavigna Silvia, Gigantino Vincenzo, Luce Amalia, Cantile Monica, Cerrone Margherita, Facchini Gaetano, Perdonà Sisto, Pignata Sandro, Di Lorenzo Giuseppe, Chieffi Sergio, Vitale Giovanni, De Sio Marco, Sgambato Alessandro, Botti Gerardo, Yousif Ali Munaim, Novellino Ettore, Grieco Paolo, Caraglia Michele
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
J Exp Clin Cancer Res. 2014 Jun 3;33(1):48. doi: 10.1186/1756-9966-33-48.
Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC)/invasive have different gene profile and clinical course. NMIBC prognosis is not completely predictable, since the relapse rate is higher than 20%, even in the form of MIBC. The aim of this study is to evaluate if UTR expression can discriminate between NMIBC and MIBC and predict the risk of relapses in NMIBCs.
We have investigated upon urotensin-II (UII) receptor (UTR) expression in vivo in 159 patients affected by NMIBC. The biological role of UTR was also investigated in vitro. UTR expression was evaluated in a tissue-micro-array, consisting of normal, NMIBC and invasive bTCC samples.
UTR discriminated between NMIBC and MIBC and showed a significant correlation between low UTR expression and shorter disease free survival in NMIBC. The superagonist UPG84 induced growth suppression at nM concentrations on 3/4 cell lines. Bladder cancer cell treatment with the antagonist urantide or the knock-down of UTR with a specific shRNA significantly blocked both the motility and invasion of bladder cancer cells.
The evaluation of UTR expression can discriminate between NMIBC at high and low risk of relapse. Moreover, our data suggest that UTR is involved in the regulation of motility, invasion and proliferation of bladder cancer cells. High UTR expression is an independent prognostic factor of good prognosis for NMIBC regulating motility and invasion of bladder cancer cells.
非肌层浸润性膀胱移行癌(NMIBC)和肌层浸润性膀胱移行癌(MIBC)/浸润性癌具有不同的基因谱和临床病程。NMIBC的预后并非完全可预测,因为即使是MIBC形式,其复发率也高于20%。本研究的目的是评估尿紧张素II(UII)受体(UTR)表达是否能区分NMIBC和MIBC,并预测NMIBC的复发风险。
我们研究了159例NMIBC患者体内尿紧张素II受体(UTR)的表达情况。还在体外研究了UTR的生物学作用。在一个由正常、NMIBC和浸润性膀胱移行细胞癌(bTCC)样本组成的组织微阵列中评估UTR表达。
UTR能够区分NMIBC和MIBC,并且在NMIBC中,低UTR表达与较短的无病生存期之间存在显著相关性。超级激动剂UPG84在纳摩尔浓度下对3/4的细胞系诱导生长抑制。用拮抗剂尿降压肽处理膀胱癌细胞或用特异性短发夹RNA(shRNA)敲低UTR可显著阻断膀胱癌细胞的运动性和侵袭性。
评估UTR表达可区分复发风险高和低的NMIBC。此外,我们的数据表明UTR参与调节膀胱癌细胞的运动性、侵袭性和增殖。高UTR表达是NMIBC预后良好的独立预后因素,可调节膀胱癌细胞的运动性和侵袭性。